Agents, termed promoters, have been identified which, though noncarcinogenic per se, are able, either on mouse skin or systemically, to induce tumorigenesis when administered specifically subsequent to subcarcinogenic doses of chemicals and UV radiation. Furthermore, promoters show this activity even when administered at times long after carcinogen treatment, when DNA repair activity has been suggested to have terminated. Such observations have lead to the proposal of an ubiquitous two-stage model of carcinogenesis by chemicals. At present few promoters of environmental relevance have been identified, even though their significance is probably considerable, since they may render tumorigenic doses of carcinogens regarded per se to offer little cancer risk, and whose removal from the environment would be impracticable on physical or economic grounds. The ability of promoters to enhance carcinogen-induced mutation frequencies in cultured V79 cells, discovered in our laboratory, suggests that the latter system has considerable potential in detecting environmental agents with promoting activity. Parallel characteristics of promoter action in animals and in V79 cell culture further suggest that the latter will be valuable for examining the mechanism of action of promoters. The study will consist of three phases: a) Study of various parameters, including exogenous metabolic activating systems, determining mutation frequencies in the V79 cell mutagenesis system. b) Determination of the effect of tumor-promoting agents on carcinogen-induced mutation frequencies. c) Determination of the effect of promoters and nonpromoting analogs on biochemical parameters, implicated in tumor promotion, in V79 cells.